Details

Autor(en) / Beteiligte

• Guo, Peng
• Dong, Xue‐Yuan
• Zhao, Ke‐Wen
• Sun, Xiaodong
• Li, Qunna
• Dong, Jin‐Tang

Titel

Estrogen‐induced interaction between KLF5 and estrogen receptor (ER) suppresses the function of ER in ER‐positive breast cancer cells

Ist Teil von

• International journal of cancer, 2010-01, Vol.126 (1), p.81-89

Ort / Verlag

Hoboken: Wiley Subscription Services, Inc., A Wiley Company

Erscheinungsjahr

2010

Link zum Volltext

Quelle

Wiley Online Library Journals Frontfile Complete

Beschreibungen/Notizen

• Kruppel‐like factor 5 (KLF5) is implicated in human breast cancer by frequent genomic deletion and expressional deregulation, but the molecular mechanisms by which KLF5 affects breast tumorigenesis are still unknown. This study was conducted to examine whether and how KLF5 affects the function of estrogen receptor (ER) in breast cancer cells. Using different cell lines, we found that restored expression of KLF5 inhibited estrogen‐promoted cell proliferation in ER‐positive MCF‐7 and T‐47D cell lines but had no effect on ER‐negative SK‐BR‐3 cells. Transcriptional activity of ER was also suppressed by KLF5, as detected by using estrogen‐stimulated ER responsive element‐mediated reporter assay and expression analysis of ER target genes including c‐MYC and Cathepsin D (CSTD). Chromatin immunoprecipitation assays showed that KLF5 inhibited ERα binding to the promoter of c‐myc and CSTD. Furthermore, estrogen induced an interaction between KLF5 and ERα. These results suggest that KLF5 inhibits the function of ERα in gene regulation and cell proliferation through protein interaction that interrupts the binding of ERα to target gene promoters to prevent target gene induction.